Comparison of clinical methods with the faecal gluten immunogenic peptide to assess gluten intake in coeliac disease

Objectives: Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten free diet (GFD). In this study, recent gluten intake was measured by GIP in CD children and compared to routine clinical measures to evaluate GFD compliance. Methods: GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow-up samples at 6 and 12 months on GFD). Compliance to GFD was evaluated based on clinical assessment, tTG levels and Biagi score. Results: GIP was detectable in 16% of patients with previous CD diagnosis on GFD. BMI z-score (p=0.774), height z-score (p=0.723), haemoglobin concentration (p=0.233), age (p=0.448), gender (p=0.734) or disease duration (p=0.488) did not differ between those with detectable and non-detectable GIP. In newly diagnosed patients, on gluten containing diet, GIP was detectable in 95% of them. Following GFD initiation, GIP decreased (p<0.001); 17% and 27% had detectable levels at 6 and 12 months, respectively. Compared to GIP, the Biagi score, tTG and clinical assessment presented sensitivity of 17%, 42% and 17%. Likewise, GIP was detectable in 16%, 16%, 14% of patients evaluated as GFD compliant according to the Biagi score, tTG and clinical assessment. A combination of methods did not improve identification of patients who were non-compliant. Conclusions: Inclusion of faecal GIP measurements is likely to improve identification of GFD recent noncompliance in CD management and could be incorporated into current follow-up strategies

Alterations in intestinal microbiota of children with celiac disease at time of diagnosis and on a gluten-free diet

Background & Aims: It is not clear whether alterations in the intestinal microbiota of children with celiac disease cause the disease or are a result of disease and/or its treatment with gluten-free diet (GFD). Methods: We obtained 167 fecal samples from 141 children (20 with new-onset celiac disease, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with celiac disease) in Glasgow, Scotland. Samples were analyzed by 16S rRNA sequencing and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 of the children with new-onset CD after 6 and 12 months on GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. Results: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset celiac disease. In contrast, 2.8% (Bray-Curtis dissimilarity index, P=.025) and 2.5% (UniFrac distances, P=.027) of the variation in microbiota composition could be accounted for by the GFD. Between 3% to 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to celiac disease with high diagnostic probability. Most of the operational taxonomic units that differed between patients on GFD with new-onset celiac disease vs healthy children were associated with nutrient and food group intake (from 75% to 94%), and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. Conclusions: Although several alterations in the intestinal microbiota of children with established celiac disease appear to be effects of a GFD, there are specific bacteria that are distinct biomarkers of celiac disease. Studies are needed to determine whether these bacteria contribute to pathogenesis of celiac disease

On the Multi-Functional Behavior of Graphene-Based Nano-Reinforced Polymers

The objective of the present study is the assessment of the impact performance and the concluded thermal conductivity of epoxy resin reinforced by layered Graphene Nano-Platelets (GNPs). The two types of used GNPs have different average thicknesses, <4 nm for Type 1 and 9–12 nm for Type 2. Graphene-based polymers containing different GNP loading contents (0.5, 1, 5, 10, 15 wt.%) were developed by using the three-roll mill technique. Thermo-mechanical (Tg), impact tests and thermal conductivity measurements were performed to evaluate the effect of GNPs content and type on the final properties of nano-reinforced polymers. According to the results, thinner GNPs were proven to be more promising in all studied properties when compared to thicker GNPs of the same weight content. More specifically, the glass transition temperature of nano-reinforced polymers remained almost unaffected by the GNPs inclusion. Regarding the impact tests, it was found that the impact resistance of the doped materials increased up to 50% when 0.5 wt.% Type 1 GNPs were incorporated within the polymer. Finally, the thermal conductivity of doped polymers with 15 wt.% GNPs showed a 130% enhancement over the reference material

The gut microbiota characteristics of children with coeliac disease and the effect of treatment

Abstract not currently available

A Preliminary Study of the Influence of Graphene Nanoplatelet Specific Surface Area on the Interlaminar Fracture Properties of Carbon Fiber/Epoxy Composites

Graphene nanoplatelets (GNPs) are of particular interest to the field of nano-reinforced composites since they possess superior mechanical, fracture, thermal, and barrier properties. Due to their geometrical characteristics, high aspect ratio (AR)/specific surface area (SSA) and their planar structure, GNPs are considered as high-potential nanosized fillers for improving performance of composites. The present study investigates the effect of SSA of GNPs on fracture properties of carbon fiber reinforced polymers (CFRPs). For this reason, two nano-doped CFRPs were produced by using two types of GNPs (C300 and C500) with different SSAs, 300 and 500 m2/g, respectively. Both types of GNPs, at the same content of 0.5 wt%, were added into the epoxy matrix of composites by applying a three-roll milling technique. The nanomodified matrix was used for the manufacturing of prepregs, while the final composite laminates were fabricated through the vacuum-bag method. Mode I and II interlaminar fracture tests were carried out to determine the interlaminar fracture toughness GIC and GIIC of the composites, respectively. According to the results, the toughening effect of C500 GNPs was the strongest, resulting in increases of 25% in GIC and 33% in GIIC compared with the corresponding unmodified composites. The activation of the absorption mechanisms of C500 contributed to this outcome, which was confirmed by the scanning electron microscopy (SEM) analyses conducted in the fracture surfaces of specimens. On the other hand, C300 GNPs, due to disability to be dispersed uniformly into the epoxy matrix, did not influence the fracture properties of CFRPs, indicating that probably there is a threshold in SSA which is necessary to achieve for improving the fracture properties of CFRPs

A systematic review of microbiome-derived biomarkers for early colorectal cancer detection

ABSTRACT: Increasing evidence suggests a role of the gut microbiome in the development of colorectal cancer (CRC) and that it can serve as a biomarker for early diagnosis. This review aims to give an overview of the current status of published studies regarding the microbiome as a screening tool for early CRC detection. A literature search was conducted using PubMed and EMBASE in August 2022. Studies assessing the efficacy of microbiome-derived biomarkers based on noninvasive derived samples were included. Not relevant studies or studies not specifying the stage of CRC or grouping them together in the analysis were excluded. The risk of bias for screening tools was performed using the QUADAS-2 checklist. A total of 28 studies were included, ranging from 2 to 462 for CRC and 18 to 665 advanced adenoma patient inclusions, of which only two investigated the co-metabolome as biomarker. The diagnostic performance of faecal bacteria-derived biomarkers had an AUC ranging from 0.28-0.98 for precursor lesions such as advanced adenomas and 0.54-0.89 for early CRC. Diagnostic performance based on the co-metabolome showed an AUC ranging from 0.69 – 0.84 for precursor lesions and 0.65 – 0.93 for early CRC. All models improved when combined with established clinical early detection markers such as gFOBT. A high level of heterogeneity was seen in the number of inclusions and methodology used in the studies. The faecal and oral gut microbiome has the potential to complement existing CRC screening tools, however current evidence suggests that this is not yet ready for routine clinical use

Electrical stimulation of the splenic nerve bundle ameliorates dextran sulfate sodium-induced colitis in mice

Background: Vagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis. Methods: Cuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of β-adrenergic receptors (β-ARs). Results: Colitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of β-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes. Conclusions: Together, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD